Biochemistry (Moscow), Год журнала: 2024, Номер 89(12-13), С. 2238 - 2251
Опубликована: Дек. 1, 2024
Язык: Английский
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Янв. 23, 2024
Abstract The Hendra and Nipah viruses (HeV NiV) are zoonotic biosafety level-4 pathogens within the Paramyxoviridae family. We previously showed that their W proteins form amyloid-like fibrils in vitro . Here, we demonstrate also forms cellula cysteine residues crucial dictating ability of to fibrillate. oxidation state acts as a switch generate either amorphous aggregates or flexible fibrils. Ectopic expression HeV induces an oxidative stress were observed nuclei different cell lines, with fibrillation being impaired by substitutions. Finally, nuclear associated impairment NF-κB pathway transfected cells. This work provides experimental evidence for Henipavirus fibrillate cells first clues on functional impact. Significance Statement severe infecting humans livestock, classified among 8 highest priorities research WHO. protein, along V is virulence factor responsible antiviral response inhibition here its into occurs nucleus cells, formation dependent redox residues. sole transfection provokes production reactive oxygen species, creating suitable environment form. show enhance repression response, thus pointing new promising target.
Язык: Английский
Процитировано
3
Microbes and Infection, Год журнала: 2024, Номер 26(8), С. 105402 - 105402
Опубликована: Авг. 8, 2024
During a viral infection, several membraneless compartments with liquid properties are formed. They can be of origin concentrating proteins and nucleic acids, harboring essential stages the cycle, or cellular containing components involved in innate immunity. This is paradigm shift our understanding replication interaction between viruses
Язык: Английский
Процитировано
3
Protein Science, Год журнала: 2025, Номер 34(4)
Опубликована: Март 18, 2025
The Hendra (HeV) and Nipah (NiV) viruses are high-priority, biosafety level-4 pathogens that cause fatal neurological respiratory disease. Their P gene encodes not only the protein, an essential polymerase cofactor, but also virulence factors V W. We previously showed W protein of HeV (WHeV) forms amyloid-like fibrils one its subdomains, PNT3, fibrillates in isolation. However, fibrillation kinetics is much faster case full-length WHeV compared to suggesting another region contributes process. In this work, we identified spanning residues 2-110 (PNT1) as crucial implicated fibrillation. Through site-directed mutagenesis, combined with thioflavin T binding experiments negative-staining transmission electron microscopy, a predicted cryptic amyloidogenic (CAR) within PNT1 main driver deciphered underlying molecular mechanism. Using FTIR, enriched cross β-sheets. Sequence alignment revealed conservation CAR across Henipavirus genus enabled identification hitherto never reported pro-amyloidogenic motif. ability form was experimentally shown be common property shared by proteins. Overall, study sheds light on mechanisms calls for future studies aimed at exploring relevance newly motif valuable target antiviral approaches.
Язык: Английский
Процитировано
0
Exploration of neuroscience, Год журнала: 2025, Номер 4
Опубликована: Март 24, 2025
The SAR-CoV-2 virus has evolved to co-exist with human hosts, albeit at a substantial energetic cost resulting in post-infection neurological manifestations [Neuro-post-acute sequelae of SARS-CoV-2 infection (PASC)] that significantly impact public health and economic productivity on global scale. One the main molecular mechanisms responsible for development Neuro-PASC, individuals all ages, is formation inadequate proteolysis/clearance phase-separated amyloid crystalline aggregates—a hallmark feature aging-related neurodegenerative disorders. Amyloidogenesis during viral persistence natural, inevitable, protective defense response exacerbated by SARS-CoV-2. Acting as chemical catalyst, accelerates hydrophobic collapse heterogeneous nucleation amorphous amyloids into stable β-sheet aggregates. clearance aggregates most effective slow wave sleep, when high levels adenosine triphosphate (ATP)—a biphasic modulator biomolecular condensates—and melatonin are available solubilize removal. dysregulation mitochondrial dynamics SARS-CoV-2, particular fusion fission homeostasis, impairs proper distinct subpopulations can remedy challenges created diversion substrates away from oxidative phosphorylation towards glycolysis support replication maintenance. subsequent reduction ATP inhibition synthesis sleep results incomplete brain aggregates, leading commonly associated age-related Exogenous not only prevents dysfunction but also elevates production, effectively augmenting solubilizing effect moiety ensure timely, optimal disaggregation pathogenic prevention attenuation Neuro-PASC.
Язык: Английский
Процитировано
0
Microscopy Research and Technique, Год журнала: 2024, Номер 87(6), С. 1131 - 1145
Опубликована: Янв. 25, 2024
The nuclear export protein of the influenza A virus (NEP) is involved in many important processes life cycle. This makes it an attractive target for treatment a disease caused by virus. Previously has been shown, that recombinant variants NEP are highly prone to aggregation solution under various conditions with formation amyloid-like aggregates. In present work, amyloid nature aggregates was evidenced Congo red binding assays. Atomic force microscopy shown can form two types spherical nanoparticles, which provide alternative pathway fibrils. Type I these "fibrillogenic" spheres, formed physiological conditions, represents micelle-like particles height 10-60 nm, generate worm-like flexible fibrils diameter 2.5-4.0 length 20-500 nm and Young's modulus ~73 MPa. II size about 400-1000 at elevated temperatures, includes fractions drop-like vesicle-like particles, generating more rigid ~8 up 2 μm. hypothetical mechanism fibril via nanospherical structures suggested. RESEARCH HIGHLIGHTS: AFM revealed They
Язык: Английский
Процитировано
2
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 6981 - 6981
Опубликована: Июнь 26, 2024
In the field of virology, liquid-liquid phase separation (LLPS) has emerged as a pivotal mechanism enabling compartmentalization required for specific steps viral replication cycle [...].
Язык: Английский
Процитировано
1
ChemBioChem, Год журнала: 2024, Номер 25(24)
Опубликована: Окт. 31, 2024
Abstract Amyloidosis is characterized by the abnormal accumulation of misfolded proteins, called amyloid fibrils, leading to diverse clinical manifestations. Recent studies on amyloidogenesis SARS‐CoV‐2 protein segments have raised concerns their potential link post‐infection neurodegeneration, however, mechanisms remain unclear. Herein, we investigated structure, stability, and amyloidogenic propensity a nine‐residue segment (SK9) envelope impact neuronal α‐synuclein (αSyn) aggregation. Specifically, amino acid sequence SK9 wildtype has been modified from basic positively charged peptide (SFYVYSRVK), nearly neutral more hydrophobic (SAAVASAVK, labelled as var1), an acidic negatively (SDAVANAVK, var2). Our findings reveal that exhibited pronounced due its disordered unstable nature, while variants possessed ordered stable structures preventing formation. Significantly, demonstrated distinct effect αSyn aggregation kinetics aggregate morphology facilitate formation aggregates with enhanced resistance against enzymatic degradation. This study highlights modifying short sequences fine‐tune properties, providing insights into understanding regulating viral‐induced aggregations.
Язык: Английский
Процитировано
1
Elsevier eBooks, Год журнала: 2024, Номер unknown, С. 423 - 441
Опубликована: Ноя. 22, 2024
Процитировано
0
Elsevier eBooks, Год журнала: 2024, Номер unknown, С. 1 - 15
Опубликована: Ноя. 22, 2024
Язык: Английский
Процитировано
0
Biochemistry (Moscow), Год журнала: 2024, Номер 89(12-13), С. 2238 - 2251
Опубликована: Дек. 1, 2024
Язык: Английский
Процитировано
0